دورية أكاديمية
Signaling pathways underlying TGF-β mediated suppression of IL-12A gene expression in monocytes.
| العنوان: | Signaling pathways underlying TGF-β mediated suppression of IL-12A gene expression in monocytes. |
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| المؤلفون: | Hourani T; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Eivazitork M; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Balendran T; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Mc Lee K; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Hamilton JA; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Zhu HJ; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Iaria J; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia., Morokoff AP; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC 3050, Australia., Luwor RB; Department of Surgery, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia; Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia; Federation University, Ballarat, VIC 3350, Australia., Achuthan AA; Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: aaa@unimelb.edu.au. |
| المصدر: | Molecular immunology [Mol Immunol] 2024 Feb; Vol. 166, pp. 101-109. Date of Electronic Publication: 2024 Jan 25. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: England NLM ID: 7905289 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9142 (Electronic) Linking ISSN: 01615890 NLM ISO Abbreviation: Mol Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, Elmsford, N. Y., Pergamon Press. |
| مواضيع طبية MeSH: | Interleukin-12 Subunit p35*/metabolism , Transforming Growth Factor beta*/metabolism, Cytokines ; Gene Expression ; Interleukin-12 ; Monocytes/metabolism ; NF-kappa B/metabolism ; Signal Transduction ; Humans |
| مستخلص: | Transforming growth factor-β (TGF-β) is a pleiotropic cytokine essential for multiple biological processes, including the regulation of inflammatory and immune responses. One of the important functions of TGF-β is the suppression of the proinflammatory cytokine interleukin-12 (IL-12), which is crucial for mounting an anti-tumorigenic response. Although the regulation of the IL-12p40 subunit (encoded by the IL-12B gene) of IL-12 has been extensively investigated, the knowledge of IL-12p35 (encoded by IL-12A gene) subunit regulation is relatively limited. This study investigates the molecular regulation of IL-12A by TGF-β-activated signaling pathways in THP-1 monocytes. Our study identifies a complex regulation of IL-12A gene expression by TGF-β, which involves multiple cellular signaling pathways, such as Smad2/3, NF-κB, p38 and JNK1/2. Pharmacological inhibition of NF-κB signaling decreased IL-12A expression, while blocking the Smad2/3 signaling pathway by overexpression of Smad7 and inhibiting JNK1/2 signaling with a pharmacological inhibitor, SP600125, increased its expression. The elucidated signaling pathways that regulate IL-12A gene expression potentially provide new therapeutic targets to increase IL-12 levels in the tumor microenvironment. Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Glioblastoma; IL-12; Inflammation; Monocytes; Signaling; TGF-β |
| المشرفين على المادة: | 0 (Cytokines) 187348-17-0 (Interleukin-12) 0 (Interleukin-12 Subunit p35) 0 (NF-kappa B) 0 (Transforming Growth Factor beta) |
| تواريخ الأحداث: | Date Created: 20240126 Date Completed: 20240220 Latest Revision: 20240220 |
| رمز التحديث: | 20240220 |
| DOI: | 10.1016/j.molimm.2024.01.008 |
| PMID: | 38278031 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-9142 |
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| DOI: | 10.1016/j.molimm.2024.01.008 |